We then carried out a follow up of the antibody responses in villagers who experienced clinical malaria during the 5-month transmission season, using archived fingerprick sera collected monthly, and when available, sera on the day of the clinical malaria episode. Transient

fluctuations were observed, with in some cases boosting of a pre-existing response (see a representative example in Kinase Inhibitor Library molecular weight Figure 9A), in others a decrease in antibodies (idem Figure 9B) or evidence of a short-lived response (idem Figure 9C). This was also observed in children experiencing multiple clinical episodes during that same time period (idem Figure 9D). In nine out of 10 subjects in whom peripheral blood parasites

collected at diagnosis of the clinical malaria episode were genotyped, the three allelic families were detected, and one individual harboured only Z IETD FMK 2 allelic families. In all 10 cases, infection with an allele against which there was no evidenced pre-existing response did not elicit any long lasting novel antibody specificity. Figure 9 Temporal fluctuation of MSP1 block2- specific CP-690550 cell line IgG during the 1998 rainy season. Antibodies were assayed on 16 pools of biotinylated peptides (sequence and composition of the pools described in Table 5). Typical individual patterns are shown, with the dates of blood sampling shown on each graph. A) Transient boosting of a pre-existing response in a 14 y old subject (code 11/21), who had a clinical malaria attack on 29/10/98. B) Transient loss of a pre-existing response in a 5 y old child (code 8/15), who had a clinical malaria attack on 28/08/98. C) Transient acquisition of a novel specificity

in a 9.5 y old child (code 02/04), Sinomenine who had a clinical malaria on 10/09/98. D) Transient changes in a 5 y old child (code 03/18), who experienced three successive clinical episodes during that time period on 17/09/98, 22/10/98 and 11/12/98. For each cinical episode, an antimalarial treatment was administered to the patient on the day of diagnosis. Long term temporal analysis of the response to MSP1-block2 To analyse antibody patterns over several years, we used archived systematic blood samples collected during the longitudinal survey. Confirming a previous study in this village [27], once acquired, the response to MSP1-block2 was essentially fixed over time. A typical example is shown in Figure 10, where a 6-year follow-up was carried out on child 01/13, starting at 6 months of age. The child had been exposed to a mean of 200 infected bites each year over the six years. A single peptide pool was recognised by this child from the age of 2.5 years onwards (Figure 10A). The intensity of the signal fluctuated subsequently, including a drop during malaria attacks [e.g.